PMID- 1700346
OWN - NLM
STAT- MEDLINE
DCOM- 19901207
LR  - 20131121
IS  - 0161-813X (Print)
IS  - 0161-813X (Linking)
VI  - 11
IP  - 2
DP  - 1990 Summer
TI  - Risk assessment for neurotoxic effects.
PG  - 211-8
AB  - Regulation of neurotoxicants is generally based on setting allowable doses 
      (exposures) by dividing a no observed adverse effect level (NOAEL) by uncertainty 
      factors that hopefully account for interspecies and intraspecies differences for 
      extrapolations of experimental results obtained in animals to humans. This 
      procedure makes no use of estimates of risk as a function of dose or does it 
      acknowledge any risk at the NOAEL. The purpose of this paper is to illustrate how 
      bioassay data can be used to estimate the risk of neurotoxic effects as a 
      function of dose. In the absence of direct measurements of neurotoxic effects, 
      biomarkers associated with neurotoxic effects can be used as measures of 
      toxicity. In the absence of a definition of an adverse effect, an abnormal level 
      for a measure of toxicity can be established which occurs only in a small 
      fraction of a population which is not exposed to the substance under 
      investigation. Risk is defined as the proportion of a population whose levels of 
      a measure of toxicity equal or exceeds the abnormal level of the measure under 
      study. The procedure is illustrated using data for neurochemical, 
      neurohistological, and behavioral effects of methylenedioxymethamphetamine (MDMA) 
      administered to rats or monkeys. This procedure is more versatile than the 
      NOAEL/uncertainty factor approach since it provides estimates of risk as a 
      function of dose of a potential neurotoxic substance.
FAU - Gaylor, D W
AU  - Gaylor DW
AD  - National Center for Toxicological Research, Jefferson, Arkansas 72079.
FAU - Slikker, W Jr
AU  - Slikker W Jr
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Designer Drugs)
RN  - 333DO1RDJY (Serotonin)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/analogs & derivatives/toxicity
MH  - Animals
MH  - Axons/drug effects
MH  - Designer Drugs/toxicity
MH  - Female
MH  - Hippocampus/metabolism
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Macaca mulatta
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Nervous System Diseases/*chemically induced
MH  - Rats
MH  - Rats, Inbred Strains
MH  - *Risk
MH  - Serotonin/metabolism
EDAT- 1990/01/11 19:15
MHDA- 2001/03/28 10:01
CRDT- 1990/01/11 19:15
PHST- 1990/01/11 19:15 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1990/01/11 19:15 [entrez]
PST - ppublish
SO  - Neurotoxicology. 1990 Summer;11(2):211-8.